CN106749006A - It is a kind of（2 hydroxyl-oxethyls）The preparation method of the alcohol of quinoline 4 - Google Patents
It is a kind of（2 hydroxyl-oxethyls）The preparation method of the alcohol of quinoline 4 Download PDFInfo
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- CN106749006A CN106749006A CN201710014568.2A CN201710014568A CN106749006A CN 106749006 A CN106749006 A CN 106749006A CN 201710014568 A CN201710014568 A CN 201710014568A CN 106749006 A CN106749006 A CN 106749006A
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- China
- Prior art keywords
- prepare compound
- reaction prepare
- hydroxyl
- solvent
- oxethyls
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- 0 CC(c(c(*)c1)cc(OCCO)c1OCCO)=O Chemical compound CC(c(c(*)c1)cc(OCCO)c1OCCO)=O 0.000 description 2
- KDNMELBHPRJLOD-UHFFFAOYSA-N OCCOc(c(OCCO)cc1ncc2)cc1c2O Chemical compound OCCOc(c(OCCO)cc1ncc2)cc1c2O KDNMELBHPRJLOD-UHFFFAOYSA-N 0.000 description 2
- ZCGJAKDLYCIJND-UHFFFAOYSA-N CC(c(cc1)cc(OCCO)c1OCCO)=O Chemical compound CC(c(cc1)cc(OCCO)c1OCCO)=O ZCGJAKDLYCIJND-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparation method of (2 hydroxyl-oxethyl) alcohol of quinoline 4, with 1 (3,4 pairs of (2 hydroxyl-oxethyl) phenyl) ethyl ketone be initiation material, target product is obtained by nitrification, reduction, cyclization, the compound is important medicine intermediate.
Description
Technical field
The present invention relates to a kind of novel processing step of medicine intermediate, more particularly to a kind of (2- hydroxyl-oxethyls) quinoline
The preparation method of quinoline -4- alcohol.
Technical background
Compound (2- hydroxyl-oxethyls) quinoline -4- alcohol, structural formula is：
The derivative of this compound (2- hydroxyl-oxethyls) quinoline -4- alcohol and correlation has in pharmaceutical chemistry and organic synthesis
It is widely used.The synthesis of (2- hydroxyl-oxethyls) quinoline -4- alcohol is more difficult at present.Accordingly, it would be desirable to it is easy to develop a raw material
, it is easy to operate, react easily controllable, the suitable synthetic method of overall yield.
The content of the invention
The invention discloses the method that one kind prepares (2- hydroxyl-oxethyls) quinoline -4- alcohol, with 1- (3,4- double (2- hydroxyls
Ethyoxyl) phenyl) ethyl ketone be initiation material, by nitrification, reduction, cyclization obtain target product 4, synthesis step is as follows：
(1), for initiation material, 2 are obtained by nitration reaction with 1- (3,4- double (2- hydroxyl-oxethyls) phenyl) ethyl ketone；
(2) reduction reaction is carried out 2, obtains 3；
(3) carry out ring closure reaction 3 and obtain 4；
One preferred embodiment in, reagent used by described nitration reaction prepare compound 2 is selected from concentrated nitric acid；Institute
The reducing agent used by reduction reaction prepare compound 3 stated is selected from palladium carbon-hydrogen；The described institute of ring closure reaction prepare compound 4
Alkali is selected from sodium.
One preferred embodiment in, solvent used by described nitration reaction prepare compound 2 is selected from acetic acid；It is described
Reduction reaction prepare compound 3 used by solvent be selected from methyl alcohol；Solvent choosing used by described ring closure reaction prepare compound 4
From ethanol.
One preferred embodiment in, the reaction temperature used by described ring closure reaction prepare compound 2 is room temperature；Institute
The temperature used by reduction reaction prepare compound 3 stated is room temperature；Used by described ring closure reaction prepare compound 4 is solvent
Reflux temperature.
The present invention relates to a kind of preparation method of (2- hydroxyl-oxethyls) quinoline -4- alcohol, currently without other Patents
Document report.
The present invention is further described by the following embodiment, and these descriptions are not present invention to be made into one
The restriction of step.It should be understood by those skilled in the art that the equivalent made to technical characteristic of the invention, or change accordingly
Enter, still fall within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of 1- (double (2- the hydroxyl-oxethyls) -2- nitrobenzophenones of 4,5-) ethyl ketone
29g 1- (3,4- double (2- hydroxyl-oxethyls) phenyl) ethyl ketone is added in 260ml acetic acid, the dense nitre of 62g is added
Acid, is stirred overnight at room temperature, and concentration adds ethyl acetate and water, point liquid, drying, concentration, the isolated 31g of residue upper prop
1- (double (2- the hydroxyl-oxethyls) -2- nitrobenzophenones of 4,5-) ethyl ketone.
(2) synthesis of 1- (double (2- hydroxyl-oxethyls) phenyl of 2- amino -4,5-) ethyl ketone
30g 1- (4,5- double (2- hydroxyl-oxethyls) -2- nitrobenzophenones) ethyl ketone is added in 240ml absolute methanols, then
The palladium carbons of 4g 10% are added, hydrogen is passed through, is stirred at room temperature 4 hours, filtered, collect filtrate, be concentrated to give 22g 1- (2- amino -4,5-
Diethyl phenyl) ethyl ketone.
(3) synthesis of (2- hydroxyl-oxethyls) quinoline -4- alcohol
12g sodium is added in 230ml absolute ethyl alcohols, then 20g 1- (2- amino -4,5- diethyl phenyls) ethyl ketones and 32g
Ethyl formate, is heated to reflux stirring 9 hours, concentrates, and adds ethyl acetate and the aqueous solution, and an extraction point liquid is dried, concentrated, remaining
Silica gel post separation obtains 8g (2- hydroxyl-oxethyls) quinoline -4- alcohol on thing.
Claims (6)
1. a kind of preparation method of (2- hydroxyl-oxethyls) quinoline -4- alcohol, with 1- (3,4- double (2- hydroxyl-oxethyls) phenyl) second
Ketone is initiation material, and target product 4 is obtained by nitrification, reduction, cyclization, and synthetic route is as follows,
2. method according to claim 1, it is characterized by described 3 steps reaction is,
(1), for initiation material, 2 are obtained by nitration reaction with 1- (3,4- double (2- hydroxyl-oxethyls) phenyl) ethyl ketone；
(2) reduction reaction is carried out 2, obtains 3；
(3) carry out ring closure reaction 3 and obtain 4；
3. method according to claim 1, it is characterised in that the reagent used by described nitration reaction prepare compound 2 is selected from
One or two mixture in concentrated nitric acid, fuming nitric aicd；Reducing agent choosing used by described reduction reaction prepare compound 3
From in sodium borohydride, potassium borohydride, lithium borohydride, sodium cyanoborohydride, lithium aluminium hydride, borine, iron powder, zinc powder, palladium carbon-hydrogen
The mixture of one or more；Alkali used by described ring closure reaction prepare compound 4 be selected from sodium, sodium hydrogen, NaOH,
In potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, triethylamine, sodium acid carbonate, pyridine, triisopropylamine, saleratus
The mixture of one or more.
4. method according to claim 1, it is characterised in that the solvent used by described nitration reaction prepare compound 2 is selected from
Methyl alcohol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,
The mixture of one or more in dinethylformamide, DMAC N,N' dimethyl acetamide, acetic acid, chloroform；Described reduction is anti-
The solvent used by prepare compound 3 is answered to be selected from methyl alcohol, ethanol, normal propyl alcohol, isopropanol, tetrahydrofuran, dichloromethane, toluene, neighbour
In dimethylbenzene, paraxylene, meta-xylene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, water one or more
Mixture；Solvent used by described ring closure reaction prepare compound 4 is selected from methyl alcohol, ethanol, normal propyl alcohol, isopropanol, tetrahydrochysene furan
Mutter, dichloromethane, toluene, ortho-xylene, paraxylene, meta-xylene, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide
In the mixture of one or more.
5. method according to claim 1, it is characterised in that the reaction temperature used by described nitration reaction prepare compound 2
It is the reflux temperature of 0 DEG C~solvent；Temperature used by described reduction reaction prepare compound 3 is the backflow temperature of 0 DEG C~solvent
Degree；Used by described ring closure reaction prepare compound 4 be 0 DEG C~solvent reflux temperature.
6. method according to claim 1, it is characterised in that the reaction temperature used by described ring closure reaction prepare compound 2
It is room temperature；Temperature used by described reduction reaction prepare compound 3 is room temperature；The described institute of ring closure reaction prepare compound 4
It is the reflux temperature of solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710014568.2A CN106749006A (en) | 2017-01-09 | 2017-01-09 | It is a kind of（2 hydroxyl-oxethyls）The preparation method of the alcohol of quinoline 4 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710014568.2A CN106749006A (en) | 2017-01-09 | 2017-01-09 | It is a kind of（2 hydroxyl-oxethyls）The preparation method of the alcohol of quinoline 4 |
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| Publication Number | Publication Date |
|---|---|
| CN106749006A true CN106749006A (en) | 2017-05-31 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710014568.2A Pending CN106749006A (en) | 2017-01-09 | 2017-01-09 | It is a kind of（2 hydroxyl-oxethyls）The preparation method of the alcohol of quinoline 4 |
Country Status (1)
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| CN (1) | CN106749006A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104326977A (en) * | 2014-10-15 | 2015-02-04 | 湖南华腾制药有限公司 | Preparation method of 6,7-diethyl-4-hydroxyquinoline |
-
2017
- 2017-01-09 CN CN201710014568.2A patent/CN106749006A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104326977A (en) * | 2014-10-15 | 2015-02-04 | 湖南华腾制药有限公司 | Preparation method of 6,7-diethyl-4-hydroxyquinoline |
Non-Patent Citations (2)
| Title |
|---|
| FLORENCE CHUNG，ET AL.: "NMR-Guided Fragment-Based Approach for the Design of tRNALys3 Ligands", 《ANGEW.CHEM.》 * |
| ISAMU MAEBA，ET AL.: "Cinnoline Chemistry.XIV.3-Cyclohexylcinnolines(1)", 《J.HETEROCYCLIC CHEM.》 * |
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Application publication date: 20170531 |
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